CORE 1: Genetically Engineered Mice for Collaborations

核心 1：用于协作的基因工程小鼠

• 批准号: 7495156
• 负责人: SUSUMU TONEGAWA
• 金额: $ 27万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7495156
• 关键词: Arts; Chimeric Proteins; Collaborations; Dominant-Negative Mutation; Dorsal; Engineering; Excitatory Synapse; Generations; Genes; Genetic Recombination; Genetically Engineered Mouse; Hippocampus (Brain); Individual; Instruction; Interdisciplinary Study; Knockout Mice; Laboratories; Learning; Memory; Monkeys; Mouse Strains; Mus; Mutant Strains Mice; N-Methyl-D-Aspartate Receptors; NR1 gene; Neurosciences Research; Prosencephalon; Pyramidal Cells; Role; Synaptic plasticity; System; Technology; Tetracycline; Tetracyclines; Training; Trans-Activators; Transgenic Mice; Transgenic Organisms; Visual Cortex; cell type; dentate gyrus; entorhinal cortex; granule cell; human NR1 protein; receptive field; receptor; tool

Many Individual Projects of the proposed Silvio O. Conte Center for Neuroscience Research (CCNR) at MIT utilize genetically engineered mice as key experimental tools. Most of these mouse strains are conditionally engineered (i.e., spatially and/or temporally restricted) and, hence, require state-of-the-art technology. The role of Core #1 is twofold: to provide the technical knowhow regarding the transgenics and knockout mice to the Center's individual laboratories and to generate some of the strains that are proposed to be used by the Center's multiple laboratories as multidisciplinary collaborations. In Specific Aims #1 to #3, the Cre-loxP recombination system will be combined with the tetracycline-transactivator (tTA) system to accomplish cell type-restricted, reversibly regulatable expression of a gene. Specific Aim #1 will attempt to regulate the NMDA receptor (NR)-1 gene in the dentate gyrus (DG) granule cells, while Specific Aim #2 will seek to regulate the GluR6 (G6) gene in the DG granule cells or CA3 pyramidal cells. These mutant mice provide invaluable tools in the Center's collaborative attempt (Individual Project #2) to understand the roles of synaptic plasticity in distinct hippocampal excitatory synapses in specific aspects of learning and memory. Specific Aim #3 will attempt to regulate the NR1 gene in the superficial layers of the entorhinal cortex and will serve the Center's collaborative effort (Individual Project #1) to understand the role of these receptors in place field formation. The objective of Specific Aim #4 is to produce a dorsal forebrain-restricted tTA mouse which is an important component mouse for the generation of multiple transgenic strains needed in the Center's collaborative attempt to understand how synaptic plasticity in the visual cortex subserves the receptive field plasticity (Individual Project #6). Core #1 will also provide training and the facility to Individual Project #7 which proposes to generate transgenic lines of PSD-GFP fusion proteins to study the morphological changes accompanying synaptic plasticity (Individual Project #7). Finally, Core #1 will provide advice and instructions to the attempt to genetically manipulate cortical function of monkeys (Individual Project #3).

麻省理工学院Silvio O. Conte神经科学研究中心（CCNR）的许多个人项目都利用基因工程小鼠作为关键的实验工具。大多数这些小鼠品系是有条件地改造的（即空间和/或时间上的限制），因此需要最先进的技术。核心1的作用是双重的：向中心的各个实验室提供有关转基因和基因敲除小鼠的技术知识